Abstract Imbalanced nutrition such as a high-fat/high-carbohydrate diet, is associated with negative effects on human health. The composition and metabolic activity of the human gut microbiota are closely related to the type of diet and have been shown to significantly change in response to changes in food content and food supplement administration. Alkylresorcinols (ARs) are lipophilic molecules that have been found to improve lipid metabolism and glycemic control and decrease systemic inflammation. Furthermore, alkylresorcinol intake is associated with changes in intestinal microbiota metabolic activity. However, the exact mechanism through which alkylresorcinols modulate microbiota activity and host metabolism has not been determined. In this study, alterations in the small intestinal microbiota (SIM) and the large intestinal microbiota (LIM) in mice fed a high-fat diet with or without pentadecylresorcinol (C15) supplementation were investigated. High-throughput sequencing was applied for jejunal and colonic microbiota analysis. The results revealed that supplementation of C15 in combination with a high-fat diet could decrease blood glucose levels. High-throughput sequencing analysis indicated that C15 intake significantly increased (p < 0.0001) the abundance of the probiotic bacteria Akkermansia muciniphila and Bifidobacterium pseudolongum both in the small and large intestines and increased the alpha diversity of LIM (p < 0.05), but not SIM. The preliminary results suggested that one of the mechanisms of the protective effects of alkylresorcinol on a high-fat diet is the modulation of the content of SIM and LIM and metabolic activity to increase the probiotic bacteria that alleviate unhealthy metabolic changes in the host.

The article presents the results of analysis of issue of disability because of ovarian cancer in female population of the Chechen Republic. The object of study was total number of women, for the first time and repeatedly recognized as disabled ones. The analysis was applied to three age groups (the young, the middle aged and the elderly) in 2014-2020. It is established that dynamics of disability was characterized by negative trends of increasing of number of the disabled. The clear-cut age differentiation was revealed:the elderly disabled predominated. The study established that the disabled suffer of persistent malfunction of blood circulation system and of immune system that resulted in such life activity limitations as moving, self-service and work functions. The characteristics of structure of ovarian cancer disability according its severity were established. The disabled with second group of disability prevailed in all age groups. At that, percentage of women with first group of disability was higher in the middle-aged disabled. The results of the study testify actuality of optimization of onco-gynecological screening of female population for the purpose of early detection of risk factors and diagnosis of malignant process at initial stages of development. This is rational way to organ-preserving treatment and medical and social prevention of primary ovarian cancer disability. The results of the study can consider as scientific practical base for both targeted routing of preventive and therapeutic and rehabilitation measures.

BACKGROUND: Stroke is a global health problem and the second leading cause of death worldwide, with ischemic stroke accounting for the majority of acute cerebrovascular accidents. Predicting outcomes in patients with ischemic stroke is challenging due to the limited prognostic performance of existing models. The lack of reliable and predictive biomarkers of ischemic stroke used in clinical practice provides a rationale for studies to address this issue.
 AIM: The aim of this study was to identify clinical, demographic, neuroimaging and molecular biomarkers of ischemic stroke associated with the fatal outcome of the disease.
 MATERIALS AND METHODS: We retrospectively analyzed cases of ischemic stroke confirmed by computed tomography of the brain with a duration of 3 months or less. As factors potentially related to the outcome of ischemic stroke, we considered (1) clinical and demographic characteristics, including sex, age, history of acute cerebrovascular accident, time from stroke to hospitalization, phase and type of stroke, neurological status on admission (level of consciousness, FOUR coma scale), comorbidities (diabetes mellitus, infectious complications, oncological diseases); (2) molecular biomarkers including blood glucose and neuron-specific enolase (NSE) levels at different phases of stroke; (3) neuroimaging biomarkers such as number and location of stroke lesion, total infarct volume, signs of edema, hemorrhagic component according to computed tomography.
 RESULTS: 38 patients with ischemic stroke were included in the study. Lesion volume was larger in non-survivors: 123 [44.6–206.2] versus 42.7 [8.2–88.7] ml3 (p=0.032), and cerebral edema was detected significantly more often on admission CT scan than in survivors: 7 (77.8%) versus 10 (34.5%), p=0.022. Stroke lesion volume was a predictor of mortality (AUC 0.739; 95% CI 0.542–0.937; p=0.032). The optimal cut-off for stroke lesion volume was found to be 90 ml3.
 CONCLUSION: Signs of edema/brain stem dislocation and cerebral lesion volume 90 ml3 documented at hospital admission are predictors of fatal outcome. Therefore, neuroimaging biomarkers can be used for risk stratification of fatal outcome in ischemic stroke patients.

IntroductionLaser doppler flowmetry (LDF) allows non-invasive assessment of microvascular functions. The combination of LDF with an occlusion functional test enables study of post-occlusive reactive hyperemia (PORH), providing additional information about vasomotor function, capillary blood flow reserve, and the overall reactivity of the microvascular system. AimTo identify early alterations of PORH variables in the skin of a rat in hemorrhagic shock (HS). Material and methodsMale Wistar rats (n = 14) weighing 400–450 g were anesthetized with a combination of tiletamine/zolazepam (20 mg/kg) and xylazine (5 mg/kg). The animals breathed on their own, and were placed on a heated platform in the supine position. A PE-50 catheter was inserted into the carotid artery to measure the mean arterial pressure (MAP). The optical probe of the Laser Doppler device was installed on the plantar surface of the hind limb of a rat; a pneumatic cuff was applied proximal to the same limb. The occlusion time was 3 min. The following physiological variables were measured at baseline and 30 min after blood loss: MAP, mmHg; mean cutaneous blood flow (M, PU); cutaneous vascular conductance (CVC = M/MAP); peak hyperemia (Mmax, PU) and maximum cutaneous vascular conductance (CVCmax) during PORH. In the HS group (n = 7), 30 % of the estimated blood volume was taken within 5 min. There was no blood loss in the group of sham-operated animals (Sham, n = 7). The results are presented as Me [25 %;75 %]. The U-Mann-Whitney criterion was used to evaluate intergroup differences. Differences were considered statistically significant at p < 0.05. ResultsThe groups did not differ at baseline. Blood loss led to a significant decrease in MAP (43 [31;46] vs. 94 [84;104] mmHg), M (11.5 [16.9;7.8] vs 16.7 [20.2;13.9]) and Mmax (18.1 [16.4;21.8] vs. 25.0 [23.0;26.2]) in the HS group compared to the Sham group, respectively. At the same time, both CVC (0.25 [0.23;0.30] vs. 0.16 [0.14;0.21]) and CVCmax (0.55 [0.38;0.49] vs 0.24 [0.23; 0.29]) increased after blood loss in the HS group compared to the Sham group. Arterial blood gas analysis revealed metabolic lactic acidosis in the HS group. ConclusionIn this rat model of HS, alterations in cutaneous blood flow are manifested by a decrease in perfusion (M) and the intensity of PORH (Mmax) with a simultaneous increase in vascular conductance (CVC and CVCmax).

Metastatic processes remain the main cause of deaths in oncology. Methods of anesthesia, in particular regional anesthesia, are considered as potential modulators of the immune response and metastatic spread. The ambiguity of the available data on the effect of regional and general anesthesia on metastatic spread is partly due to the fact that general anesthetic in combined anesthesia is quite often not taken into account, and this, in turn, masks the possible influence of regional anesthesia.The purpose of this meta-analysis was to make a comparative assessment of the effect of general anesthesia and general anesthesia in combination with regional anesthesia on the relapse-free and overall survival of cancer patients after surgery.Materials and methods. We analyzed 8 randomized controlled trials involving 1822 patients and comparing the groups of cancer patients who were operated either under general anesthesia (total intravenous (TIVA) or inhalation (IA)), or general anesthesia in combination with regional anesthesia (TIVA+RA or IA+RA, respectively). Trial using combinations of inhaled and intravenous anesthetics was excluded from the analysis for a more accurate assessment of the effect of regional anesthesia. The study complies with the recommendations of the Cochrane Community and PRISMA standards. The protocol was registered on the INPLASY platform. We used PubMed, Google Scholar and CENTRAL databases. We used a subgroup analysis and GRADE tool to assess the quality of evidence.Results. There were no statistically significant differences in relapse-free and overall survival when comparing different anesthesia methods. For a relapse-free survival, comparing TIVA vs TIVA+RA resulted in no significant difference : OR=1.20 [95% CI 0.92-1.55]; when IA vs IA+RA were compared, OR=1.10 [95% CI 0.94-1.29]. Similar results were obtained for overall survival.Conclusion. Based on the meta-analysis results, regional anesthesia had no effect on relapse-free and overall survival in oncosurgery patients.

The human microbiota produces metabolites that can enter the bloodstream and exert systemic effects on various functions in both healthy and pathological states. We have studied the participation of microbiota-related metabolites in bacterial infection by examining their influence on the activity of cyclooxygenase (COX) as a key enzyme of inflammation. The influence of aromatic microbial metabolites, derivatives of phenylalanine (phenylpropionic acid, PPA), tyrosine (4-hydroxyphenyllactic acid, HPLA), and tryptophan (indolacetic acids, IAA), the concentrations of which in the blood change notably during sepsis, was evaluated. Also, the effect of itaconic acid (ITA) was studied, which is formed in macrophages under the action of bacterial lipopolysaccharides (LPS) and appears in the blood in the early stages of infection. Metabiotic acetyl phosphate (AcP) as a strong acetylating agent was also tested. The activity of COX was measured via the TMPD oxidation colorimetric assay using the commercial pure enzyme, cultured healthy monocytes, and the human acute monocytic leukemia cell line THP-1. All metabolites in the concentration range of 100-500 μM lowered the activity of COX. The most pronounced inhibition was observed on the commercial pure enzyme, reaching up to 40% in the presence of AcP and 20-30% in the presence of the other metabolites. On cell lysates, the effect of metabolites was preserved, although it significantly decreased, probably due to their interaction with other targets subject to redox-dependent and acetylation processes. The possible contribution of the redox-dependent action of microbial metabolites was confirmed by assessing the activity of the enzyme in the presence of thiol reagents and in model conditions, when the COX-formed peroxy intermediate was replaced with tert-butyl hydroperoxide (TBH). The data show the involvement of the microbial metabolites in the regulation of COX activity, probably due to their influence on the peroxidase activity of the enzyme.

The profile of and dynamic concentration changes in tyrosine, phenylalanine, and tryptophan metabolites in blood are of great interest since they could be considered potential biomarkers of different disorders. Some aromatic metabolites, such as 4-hydroxyphenyllactic, 4-hydroxyphenylacetic, phenyllactic, and 4-hydroxybenzoic acids have previously demonstrated their diagnostic significance in critically ill patients and patients with post-COVID-19 syndrome. In this study, a sensitive method, including serum protein precipitation with methanol and ultra-high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection, was developed and validated for six phenyl- and five indole-containing acids in human serum. The liquid-liquid extraction was also examined, but it demonstrated unsatisfactory results based on analyte recoveries and the matrix effect. However, the recoveries for all analytes reached 100% and matrix effects were not observed using protein precipitation. This made it possible to use deionized water as a blank matrix. The lower limits of quantitation (LLOQs) were from 0.02 to 0.25 μmol/L. The validated method was used for the analysis of serum samples of healthy volunteers (n = 48) to reveal the reference values of the target analytes. The concentrations of the most clinically significant metabolite 4-hydroxyphenyllactic acid, which were revealed using UPLC-MS/MS and a previously developed gas chromatography-mass spectrometry method, were completely comparable. The proposed UPLC-MS/MS protocol can be used in the routine clinical practice of medical centers.

INTRODUCTION: Severe combined trauma remains the leading cause of mortality and disability of the workable population. Under damaging factor influence, a whole cascade of pathological processes is triggered, leading to development of multiple organ failure. OBJECTIVE: Exploration of the effects synthetic analogue of tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine diacetate (Dalargin) on the dynamics of oxidative stress markers in patients with severe polytrauma and the development of organ dysfunction. MATERIALS AND METHODS: 104 patients with severe combined trauma were included in study. There were 38 patients in the Dalargin group and 66 patients in the control group. Patients from main group received Dalargin in the form of a constant infusion through a syringe dispenser at the dose of 10 mcg/kg/hour at first 12 hours of hospitalization and 5 mcg/kg/hour up to 72 hours from the moment of admission. The control group received standard treatment. Indicators of oxidative stress were evaluated at the time of admission (0 days), 1, 3, 5, 7, 10 and 14 days from the therapy onset. RESULTS: In the main group, there was a significant decrease in oxidative stress markers such as malondialdehyde from the first day of treatment (p &lt; 0.05), normalization of stable nitric oxide metabolites at day 10, and a decrease in total antioxidant activity below normal throughout the observation period. Mortality was comparable in both groups (p &gt; 0.05), but the length of hospital stay was lower in surviving patients in the Dalargin group (p &lt; 0.05). The development of organ dysfunction (acute respiratory distress syndrome, acute kidney injury) was less frequent in the Dalargine group (p &lt; 0.05), but infectious complications (pneumonia, meningitis, wound suppuration) were comparable. CONCLUSIONS: Dalargin leads to a decrease of oxidative stress markers and normalization of endothelial function indicators, which contributes to a decrease of organ dysfunction frequency.

Clinical orthostatic hypotension (OH) and hypertension (OHT) are risk factors for arterial hypertension (AH) and cardiovascular diseases (CVD) and are associated with increased vascular stiffness. Preclinical OH and OHT are poorly understood. The main objective was to investigate preclinical orthostatic abnormalities and their association with increased vascular stiffness in different age groups of adults. A specially designed head-up tilt test standardized for hydrostatic column height was used to detect them. Three age groups of clinically healthy subjects were examined. In the group of young adults up to 30 years old, a significant predominance of orthostatic normotension (ONT) and an insignificant number of subjects with preclinical OH and OHT were found. In the age group over 45 years, compared to the group under 30 years, there was a twofold decrease in the proportion of individuals with ONT and a significant increase with preclinical OH and OHT. In all age groups, there was a significant orthostatic increase in vascular stiffness (as measured by the brachial-ankle pulse wave velocity (baPWV), which was recovered to the baseline level when returning to the supine position. Overall, subjects with preclinical OH and OHT had significantly higher baPWV values compared to those with ONT (p = 0.001 and p = 0.002, respectively), with all subjects having vascular stiffness values within normal age-related values.